Can Storage Stability and Simulated Gastrointestinal Behavior Change the Cytotoxic Effects of Concentrated Guava Leaves Extract against Human Lung Cancer Cells?

The influence of storage stability and simulated gastrointestinal behavior of different extracts of guava leaves extracts (NC: not concentrated, and C10 and C20: concentrated by nanofiltration) was evaluated based on their total phenolic compound (TPC) contents and antioxidant activity as well as on their cytotoxic effects on A549 and Vero cells. The results showed that C10 and C20 presented high stability for 125 days probably due to their high TPC contents and antioxidant activity. The simulated gastrointestinal behavior modified their TPC contents; however, after all digestion steps, the TPC values were higher than 70%, which means that they were still available to exert their bioactivities. Additionally, the cytotoxic effects of these extracts were evaluated before and after the simulated gastrointestinal behavior or under different storage conditions. C10 presented the best selectivity indices (SI) values (IC50 Vero cells/IC50 A549 cells) at both conditions suggesting that it can be considered a potential extract to be developed as a functional food due to its resistance to the gastrointestinal digestion and storage conditions tested.

Prevention of drug diversion and substance use disorders among anesthesiologists: a narrative review

Abstract Diversion of substances from the care of the intended patient is a significant problem in healthcare. Patients are harmed by the undertreatment of pain and suffering, transmission of disease, as well as the risk associated with impaired vigilance. Healthcare providers may be harmed by the physical and mental impact of their addictions. Healthcare systems are placed in jeopardy by the legal impact associated with illegal routes of drug release including sanction and financial liability and loss of public trust. Healthcare institutions have implemented many measures to reduce diversion from the perioperative area. These efforts include education, medical record surveillance, automated medication dispensing systems, urine drug testing, substance waste management systems, and drug diversion prevention teams. This narrative review evaluates strengths, weaknesses, and effectiveness of these systems and provides recommendations for leaders and care providers.

Prevention of drug diversion and substance use disorders among anesthesiologists: a narrative review.

Diversion of substances from the care of the intended patient is a significant problem in healthcare. Patients are harmed by the undertreatment of pain and suffering, transmission of disease, as well as the risk associated with impaired vigilance. Healthcare providers may be harmed by the physical and mental impact of their addictions. Healthcare systems are placed in jeopardy by the legal impact associated with illegal routes of drug release including sanction and financial liability and loss of public trust. Healthcare institutions have implemented many measures to reduce diversion from the perioperative area. These efforts include education, medical record surveillance, automated medication dispensing systems, urine drug testing, substance waste management systems, and drug diversion prevention teams. This narrative review evaluates strengths, weaknesses, and effectiveness of these systems and provides recommendations for leaders and care providers.

One year follow-up on a randomized study investigating serratus anterior muscle and pectoral nerves type I block to reduced neuropathic pain descriptors after mastectomy.

Breast cancer is the second most common diagnosed type of cancer in women. Chronic neuropathic pain after mastectomy occurs frequently and is a serious health problem. In our previous single-center, prospective, randomized controlled clinical study, we demonstrated that the combination of serratus anterior plane block (SAM) and pectoral nerve block type I (PECS I) with general anesthesia reduced acute postoperative pain. The present report describes a prospective follow-up study of this published study to investigate the development of chronic neuropathic pain 12 months after mastectomy by comparing the use of general anesthesia alone and general anesthesia with SAM + PECS I. Additionally, the use of analgesic medication, quality of life, depressive symptoms, and possible correlations between plasma levels of interleukin (IL)-1 beta, IL-6, and IL-10 collected before and 24 h after surgery as predictors of pain and depression were evaluated. The results showed that the use of SAM + PECS I with general anesthesia reduced numbness, hypoesthesia to touch, the incidence of patients with chronic pain in other body regions and depressive symptoms, however, did not significantly reduce the incidence of chronic neuropathic pain after mastectomy. Additionally, there was no difference in the consumption of analgesic medication and quality of life. Furthermore, no correlation was observed between IL-1 beta, IL-6, and IL-10 levels and pain and depression. The combination of general anesthesia with SAM + PECS I reduced the occurrence of specific neuropathic pain descriptors and depressive symptoms. These results could promote the use of SAM + PECS I blocks for the prevention of specific neuropathic pain symptoms after mastectomy.Registration of clinical trial: The Research Ethics Board of the Hospital Sirio-Libanes/Brazil approved the study (CAAE 48721715.0.0000.5461). This study is registered at Registro Brasileiro de Ensaios Clinicos (ReBEC), and ClinicalTrials.gov, Identifier: NCT02647385.

Effects of Lipophilicity and Structural Features on the Antiherpes Activity of Digitalis Cardenolides and Derivatives.

There is growing interest in exploring Digitalis cardenolides as potential antiviral agents. Hence, we herein investigated the influence of structural features and lipophilicity on the antiherpes activity of 65 natural and semisynthetic cardenolides assayed in vitro against HSV-1. The presence of an α,ß-unsaturated lactone ring at C-17, a ß-hydroxy group at C-14 and C-3ß-OR substituents were considered essential requirements for this biological activity. Glycosides were more active than their genins, especially monoglycosides containing a rhamnose residue. The activity enhanced in derivatives bearing an aldehyde group at C-19 instead of a methyl group, whereas inserting a C-5ß-OH improved the antiherpes effect significantly. The cardenolides lipophilicity was accessed by measuring experimentally their log P values (n-octanol-water partition coefficient) and disclosed a range of lipophilicity (log P 0.75±0.25) associated with the optimal antiherpes activity. In silico studies were carried out and resulted in the establishment of two predictive models potentially useful to identify and/or optimize novel antiherpes cardenolides. The effectiveness of the models was confirmed by retrospective analysis of the studied compounds. This is the first SAR study addressing the antiherpes activity of cardenolides. The developed computational models were able to predict the active cardenolides and their log P values.

Strategies for promoting mental health among residents: scoping review protocol.

Health professionals are encouraged to attend a residency period of two to seven years after graduating. The typical demands of this in-service training modality have been associated with reduced sleep quality, decreased exercise frequency, and detachment from family and social relationships, leading to an increased diagnosis of anxiety, depression, and burnout syndrome. Therefore, conducting a scoping review to identify strategies aimed at promoting mental health and wellbeing among residents from different health areas is essential to support any forthcoming preventive action.

Simulação de alta fidelidade no desenvolvimento de competências não técnicas dos enfermeiros do Serviço de Urgência / High fidelity simulation in the development of non-technical skills of nurses in the Emergency Service

Os eventos adversos no cuidado à pessoa em situação crítica são maioritariamente atribuídos à falha de competências não técnicas, como a comunicação e a liderança. O treino destas competências, com recurso à simulação de alta fidelidade, deve ser agregado ao processo formativo da equipa de emergência. Neste sentido, o objetivo deste estudo é analisar se o treino de competências não técnicas (comunicação e liderança) em contexto de práticas clínicas simuladas, com recurso a simulação de alta fidelidade, tem influência no conhecimento, na performance, na autoconfiança e na satisfação dos Enfermeiros do Serviço de Urgência, para atuar em situações de emergência. Trata-se de um estudo quantitativo, de carácter pré-experimental, com desenho antes-após com grupo único. Foi desenvolvido e implementado um programa de formação de práticas clínicas simuladas, com recurso a cenários de simulação de alta fidelidade, para treino de competências não técnicas (comunicação e liderança) em situações de emergência. A amostra é não probabilística por conveniência, constituída por 20 enfermeiros do Serviço de Urgência. Os resultados demonstraram uma melhoria estatisticamente significativa do conhecimento e da autoconfiança. Quanto à performance, embora a amostra tenha evidenciado uma melhoria substancial tanto na comunicação como na liderança, os resultados não foram estatisticamente significativos. Os enfermeiros demonstraram satisfação elevada com o programa de formação com recurso à simulação de alta fidelidade. A evidência que este trabalho de investigação gerou revela que o treino de competências não técnicas, comunicação e liderança, em situações de emergência, com recurso à simulação de alta fidelidade, é promissor para a melhoria da qualidade dos cuidados, segurança do doente e ganhos em saúde neste contexto. A simulação de alta fidelidade evidencia-se como um bom método pedagógico nos processos de formação profissional contínua em Enfermagem.

Development of a cell-based reporter assay for detection of Human alphaherpesviruses.

Immunosuppressed patients can suffer from Human alphaherpesvirus (HSV) infection with fast evolution, severe atypical symptomatology, and often-fatal outcome. Thus, the development and validation of new methods in vitro and in vivo to promote an early diagnosis and effective treatment of these patients are crucial. Therefore, this work aimed to develop a cell-based reporter assay for the detection of HSV through the transfection of Vero cells with the ICP10 promoter from HSV-2 linked to the pZsGreen1-1 plasmid. The assay was evaluated on Vero cells infected with HSV-1 or HSV-2 and followed by treating them with anti-HSV agents (acyclovir, gallic acid, convallatoxin, and Uncaria sp. extract) or with no anti-HSV activity agents (Passiflora edulis extract and cardenolide derivatives). The GFP expression was increased by both HSV cellular infection, which was detected by flow cytometry and fluorescence microscopy. F2R Zsgreen1-1 cells infection with 200 and 600 PFU/mL of HSV-2 increased the fluorescence intensity, when compared to the controls, by approximately 30% and 60%, respectively. Infection with 100 and 600 PFU/mL of HSV-1 also increased the fluorescence intensity by approximately 20% and 35%, when compared to the controls, respectively. The F2R ZsGreen1-1 system revealed to be an efficient assay, which can be used for clinical diagnosis, antiviral resistance evaluation, HSV cycle studies, and new antiviral drug research.

A New Saquinavir Mesylate-Sodium Decyl Sulfate Salt Discovered by Serendipity during an Anomalous Dissolution Test.

PURPOSE: To understand the anomalous behavior of Saquinavir Mesylate (SQVM) in sodium decyl sulfate (SDS) medium during a dissolution test through a crystallographic analysis of the crystal obtained. As a result, it will be possible to elucidate its crystal structure and carry out a complete solid-state characterization of the API. METHODS: The solid form obtained was characterized by a structural analysis through X-ray single crystal and powder diffraction. The crystallographic structures of the new salt and the SQVM were compared. In addition, a complete solid-state characterization of SQVM raw material was carried out by techniques such as diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), Raman spectroscopy, scanning electron microscopy and a dissolution method. RESULTS: A new salt consisting of SQVM and SDS was crystallized and its crystal structure was elucidated and reported herein for the first time. The anionic part of SDS interacts with the cationic segment of SQVM to obtain a new salt designated as SQV-DS, which precipitates. The main difference between the two structures occurs in the c-axis expansion, which increases from 15.966 (5) to 21.1924 (14), respectively. CONCLUSIONS: Some of the strategies to enhance the dissolution rate of poorly aqueous soluble APIs include the use of surfactants such as SDS in the dissolution medium, as well as in the formulated products. However, there have been constant reports of a dissolution rate slowdown by some surfactants. The interaction mechanisms between the APIs and the dissolution medium containing surfactants need to be carefully investigated in current pharmaceutical formulations. Graphical Abstract.

Noninvasive intracranial pressure real-time waveform analysis monitor during prostatectomy robotic surgery and Trendelenburg position: case report.

Both robotic surgery and head-down tilt increase intracranial pressure by impairing venous blood outflow. Prostatectomy is commonly performed in elderly patients, who are more likely to develop postoperative cognitive disorders. Therefore, increased intracranial pressure could play an essential role in cognitive decline after surgery. We describe a case of a 69-year-old male who underwent a robotic prostatectomy. Noninvasive Brain4careTM intraoperative monitoring showed normal intracranial compliance during anesthesia induction, but it rapidly decreased after head-down tilt despite normal vital signs, low lung pressure, and adequate anesthesia depth. We conclude that there is a need for intraoperative intracranial compliance monitoring since there are major changes in cerebral compliance during surgery, which could potentially allow early identification and treatment of impaired cerebral complacency.

Drug abuse amongst anesthetists in Brazil: a national survey.

BACKGROUND: The prevalence of Substance Use Disorders (SUD) and acceptance of drug testing among anesthetists in Brazil has not been determined. METHODS: An internet-based survey was performed to investigate the prevalence of SUD among anesthetists in Brazil, to explore the attitudes of anesthetists regarding whether SUD jeopardizes the health of an impaired provider or their patient, and to determine the provider's perspective regarding acceptance and effectiveness of drug testing to reduce SUD. The questionnaire was distributed via social media. REDCap was utilized to capture data. A sample size of 350 to achieve a confidence level of 95% and confidence interval of 5 was estimated. Study report was based on STROBE and CHERRIES statements. RESULTS: The survey was returned from 1,295 individuals. Most individuals knew an anesthesia provider with a SUD (82.07%), while 23% admitted personal use. The most common identified substances of abuse were opioids (67.05%). Very few respondents worked in a setting that performs drug testing (n = 17, 1.33%). Most individuals believed that drug testing could improve personal safety (82.83%) or the safety of patients (85.41%). Individuals with a personal history of SUD were less likely to believe in the effectiveness of drug testing to reduce one's own risk (74.92% vs. 85.18%, p < 0.0001) or improve the safety of patients (76.27% vs. 88.13%, p < 0.001). CONCLUSIONS: SUDs are common among anesthetists in Brazil. Drug testing would be accepted as a viable means to reduce the incidence although a larger study should be performed to investigate the logistical feasibility.

Matrix Effects of the Hydroethanolic Extract of Calyces of Physalis peruviana L. on Rutin Pharmacokinetics in Wistar Rats Using Population Modeling.

Rutin is the rutinose conjugate of quercetin. It presents several biological activities and is the major flavonoid in the hydroalcoholic extract of the calyces of Physalis peruviana L. It also shows hypoglycemic activity after oral administration. The aim of this work was to study the matrix effects of the extract from P. peruviana calyces on the pharmacokinetics of rutin and its metabolites in Wistar rats, using non-compartmental and population pharmacokinetic analyses. A pharmacokinetic study was performed after intravenous and oral administration of different doses of pure rutin and the extract. In the non-compartmental analysis, it was found that rutin from the extract exhibited higher distribution and clearance, as well as an 11-fold increase in the bioavailability of its active metabolites. A population pharmacokinetic model was also carried out with two compartments, double absorption and linear elimination, in which the extract and the doses were the covariates involved. This model correctly described the differences observed between rutin as a pure compound and rutin from the extract, including the dose dependency.

Opioids and premature biochemical recurrence of prostate cancer: a randomised prospective clinical trial.

BACKGROUND: Prostate cancer is one of the most prevalent neoplasms in male patients, and surgery is the main treatment. Opioids can have immune modulating effects, but their relation to cancer recurrence is unclear. We evaluated whether opioids used during prostatectomy can affect biochemical recurrence-free survival. METHODS: We randomised 146 patients with prostate cancer scheduled for prostatectomy into opioid-free anaesthesia or opioid-based anaesthesia groups. Baseline characteristics, perioperative data, and level of prostate-specific antigen every 6 months for 2 yr after surgery were recorded. Prostate-specific antigen >0.2 ng ml-1 was considered biochemical recurrence. A survival analysis compared time with biochemical recurrence between the groups, and a Cox regression was modelled to evaluate which variables affect biochemical recurrence-free survival. RESULTS: We observed 31 biochemical recurrence events: 17 in the opioid-free anaesthesia group and 14 in the opioid-based anaesthesia group. Biochemical recurrence-free survival was not statistically different between groups (P=0.54). Cox regression revealed that biochemical recurrence-free survival was shorter in cases of obesity (hazard ratio [HR] 1.63, confidence interval [CI] 0.16-3.10; p=0.03), high D'Amico risk (HR 1.58, CI 0.35-2.81; P=0.012), laparoscopic surgery (HR 1.6, CI 0.38-2.84; P=0.01), stage 3 tumour pathology (HR 1.60, CI 0.20-299) and N1 status (HR 1.34, CI 0.28-2.41), and positive surgical margins (HR 1.37, CI 0.50-2.24; P=0.002). The anaesthesia technique did not affect time to biochemical recurrence (HR -1.03, CI -2.65-0.49; P=0.18). CONCLUSIONS: Intraoperative opioid use did not modify biochemical recurrence rates and biochemical recurrence-free survival in patients with intermediate and high D'Amico risk prostate cancer undergoing radical prostatectomy. CLINICAL TRIAL REGISTRATION: NCT03212456.